Clinical Pharmacology Study to Evaluate the Total Systemic Exposure and Lung Bioavailability of CHF 5993 pMDI Combination in Healthy Volunteers

NCT02359292 | Completed Phase 1

• 1 other identifier: CCD-05993AB2-01
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

The study is performed to evaluate the total systemic exposure and lung bioavailability of CHF 5993 pMDI combination, in healthy volunteers subjects.

Conditions

Asthma

Outcome Measures

Primary Outcomes (2)

• Systemic exposure of B17MP, Formoterol and Glycopyrronium bromide, without charcoal block (To evaluate the total systemic exposure as AUCt and Cmax) Composite outcome measures of PK variables

  Composite outcome measures of PK variables

  over 32hours after administration

• Lung exposure of B17MP, Formoterol and Glycopyrronium bromide without charcoal block (To evaluate the lung exposure (as AUCt and Cmax) Composite outcome measures of PK variables

  Composite outcome measures of PK variables

  over 32hours after administration

Secondary Outcomes (2)

• Systemic effects of CHF5993 (To evaluate the systemic effects as potassium and glucose levels) Composite outcome measures of PD variables

  over 24hours after administration

• Systemic cardiac effects and the general safety (Composite outcome measures of cardiac variables (such as HR, BP, QT) and safety variables (such as AE, SAE)

  over 24hours after administration

Study Arms (5)

CHF 5993 HS 200/6/25 pMDI

EXPERIMENTAL

High Strength fixed combination

Drug: CHF 5993 HS 200/6/25 pMDI

CHF 5993 MS 100/6/25 pMDI

ACTIVE COMPARATOR

Medium Strength fixed combination

Drug: CHF 5993 MS 100/6/25 pMDI

CHF 5993 HS 200/6/25 pMDI + Charcoal Block

EXPERIMENTAL

High Strength fixed combination plus Charcoal Block

Drug: CHF 5993 HS 200/6/25 pMDI + Charcoal Block

CHF 5993 MS 100/6/25 pMDI + Charcoal Block

ACTIVE COMPARATOR

Medium Strength fixed combination plus Charcoal Block

Drug: CHF 5993 MS 100/6/25 pMDI + Charcoal Block

Placebo pMDI

PLACEBO COMPARATOR

Placebo

Drug: Placebo pMDI

Interventions

CHF 5993 HS 200/6/25 pMDI DRUG

CHF 5993 HS 200/6/25 pMDI

CHF 5993 MS 100/6/25 pMDI DRUG

CHF 5993 MS 100/6/25 pMDI

CHF 5993 HS 200/6/25 pMDI + Charcoal Block DRUG

CHF 5993 HS 200/6/25 pMDI + Charcoal Block

CHF 5993 MS 100/6/25 pMDI + Charcoal Block DRUG

CHF 5993 MS 100/6/25 pMDI + Charcoal Block

Placebo pMDI DRUG

Placebo pMDI

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Subject's written informed consent obtained prior to any study related procedure.
• Able to understand the study procedures, the risks involved and ability to be trained to use the devices correctly.
• Male and female subjects aged 18 to 55 years inclusive.
• Body mass index (BMI) within the range of 18 to 30 kg/m2 inclusive.
• Non- or ex-smokers who smoked \< 5 pack years (pack-years = the number of cigarette packs per day, times the number of years) and stopped smoking \> 1 year prior to screening.
• Good physical and mental status, determined on the basis of the medical history and a general clinical examination, at screening and before randomization.
• Lung function measurements within normal limits (Normal values (according to GINA 2014 document): FEV1/FVC \> 0.70 and FEV1 \> 80% predicted).
• Male subjects: they and/or their partner must be willing to use an approved method of contraception from the time of screening and until 30 days after the last dose of study. Subjects must not donate sperm for 30 days after the last dose of study drug.\*
• Female subjects: post-menopausal women having at least 12 months of natural (spontaneous) amenorrhea, or women of childbearing potential (defined as all women physiologically capable of becoming pregnant), using an acceptable method of contraception
• Surgical sterilization (i.e. bilateral tubal ligation, hysterectomy for females; vasectomy for males)
• Hormonal contraception (implantable, injectable, patch, oral)
• Double-barrier methods: condom and occlusive cap (diaphragm or cervical/vault caps)
• Placement of an intrauterine device (IUD) or intrauterine system (IUS).

You may not qualify if:

• Blood donation (equal or more than 450 ml) or blood loss, less than 8 weeks before inhalation of the study medication.
• Female subjects: pregnant or lactating women (where pregnancy is defined as the state of a female after conception and until the termination of the gestation) confirmed by a positive urine test at screening and randomization.
• Positive HIV1 or HIV2 serology.
• Positive results from the Hepatitis serology which indicates acute or chronic Hepatitis B or Hepatitis C.
• Unsuitable veins for repeated venipuncture.
• History of alcohol abuse within 12 months prior to screening.
• History of drug abuse within 12 months prior to screening (or positive urine drug test performed at screening).
• Subjects who have a positive urine test for cotinine.
• Clinically relevant abnormal laboratory values suggesting an unknown disease and requiring further clinical investigation. Note: In case of abnormal laboratory values, the test can be performed again once before randomization.
• Clinically relevant and uncontrolled hepatic, gastrointestinal, endocrine, metabolic, neurologic, or psychiatric disorder that may interfere with successful completion of this protocol.
• History of glaucoma, symptomatic prostatism or urinary retention.
• Subjects who have cardiovascular condition such as, but not limited to, unstable ischemic heart disease, NYHA Class III/IV left ventricular failure, acute ischemic heart disease in the last year prior to study screening, history of sustained cardiac arrhythmias or sustained and non-sustained cardiac arrhythmias diagnosed in the last 6 months (sustained means lasting more than 30 seconds and or ending only with external action, and or leads to hemodynamic collapse; non-sustained means \> 3 beats \< 30 seconds, and or ending spontaneously, and or asymptomatic), impulse conduction high degree blocks, ICD implant
• Abnormal ECG (i.e.: QRS \> 120 msec, PR \> 220 msec, HR \< 40 bpm, HR \> 110 bpm, QTcF \> 450 ms for males or QTcF \> 470 ms for females) at screening.
• Note: In case of abnormal ECG, the test can be performed again once before randomization.
• Clinically significant abnormal 24h-Holter monitoring at screening (if necessary the Holter evaluation can be done on another day before randomization).

Sponsors & Collaborators

• Chiesi Farmaceutici S.p.A.: lead

Study Sites (1)

SGS CPU Antwerpen

Antwerp, Belgium

Location

MeSH Terms

Conditions

Asthma

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 30, 2015
• First Posted: February 10, 2015
• Study Start: February 1, 2015
• Primary Completion: April 1, 2015
• Study Completion: July 1, 2015
• Last Updated: July 2, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)